Cannabidiol as a Therapeutic Target: Evidence of its Neuroprotective and Neuromodulatory Function in Parkinson’s Disease
Open accessAbstract
The phytocannabinoids of Cannabis sativa L. have, since ancient times, been proposed as a pharmacological alternative for treating various central nervous system (CNS) disorders. Interestingly, cannabinoid receptors (CBRs) are highly expressed in the basal ganglia (BG) circuit of both animals and humans. The BG are subcortical structures that regulate the initiation, execution, and orientation of movement. CBRs regulate dopaminergic transmission in the nigro-striatal pathway and, thus, the BG circuit also. The functioning of the BG is affected in pathologies related to movement disorders, especially those occurring in Parkinson’s disease (PD), which produces motor and non-motor symptoms that involving GABAergic, glutamatergic, and dopaminergic neural networks. To date, the most effective medication for PD is levodopa (l-DOPA); however, long-term levodopa treatment causes a type of long-term dyskinesias, l-DOPA-induced dyskinesias (LIDs). With neuromodulation offering a novel treatment strategy for PD patients, research has focused on the endocannabinoid system (ECS), as it participates in the physiological neuromodulation of the BG in order to control movement. CBRs have been shown to inhibit neurotransmitter release, while endocannabinoids (eCBs) play a key role in the synaptic regulation of the BG. In the past decade, cannabidiol (CBD), a non-psychotropic phytocannabinoid, has been shown to have compensatory effects both on the ECS and as a neuromodulator and neuroprotector in models such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and reserpine, as well as other PD models. Although the CBD-induced neuroprotection observed in animal models of PD has been attributed to the activation of the CB1 receptor, recent research conducted at a molecular level has proposed that CBD is capable of activating other receptors, such as CB2 and the TRPV-1 receptor, both of which are expressed in the dopaminergic neurons of the nigro-striatal pathway. These findings open new lines of scientific inquiry into the effects of CBD at the level of neural communication. Cannabidiol activates the PPARγ, GPR55, GPR3, GPR6, GPR12, and GPR18 receptors, causing a variety of biochemical, molecular, and behavioral effects due to the broad range of receptors it activates in the CNS. Given the low number of pharmacological treatment alternatives for PD currently available, the search for molecules with the therapeutic potential to improve neuronal communication is crucial. Therefore, the investigation of CBD and the mechanisms involved in its function is required in order to ascertain whether receptor activation could be a treatment alternative for both PD and LID.
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CBD has numerous therapeutic effects including treatment of anxiety, pain, nausea, and motor deficits including tremor in Parkinson's disease.
“CBD is the non-psychotropic component of marijuana, and there are numerous therapeutic effects of this drug including treatment of anxiety, pain, nausea, and motor deficits including the tremor in Parkinson’s disease [116].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [116]
CBD has neuromodulatory and neuroprotective effects through mechanisms including blocking neuroinflammation, potentiating anti-inflammatory pathways, improving mitochondrial function, GABAA agonist potentiation, stimulation of 5HT1A receptors, and enhancing levels of anandamide.
“CBD has both neuromodulatory and neuroprotective effects through a number of mechanisms including blocking neuroinflammation and potentiating anti-inflammatory pathways, improving mitochondrial function, GABAA agonist potentiation, stimulation of 5HT1A receptors, and enhancing levels of anandamide (AEA) [116–119].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [116]
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BackgroundCannabidiol, a novel inverse agonist for GPR12
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Flagged first, then by citations
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Sorted by citations
An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
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- Authors
- Patricio, F., Morales-Andrade, A. A., Patricio-Martínez, A., & Limón, I. D.
- Affiliations
- Benemérita Universidad Autónoma de Puebla (MX)
- Corresponding author
- Limón, Ilhuicamina Daniel
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2020-12-15
- Volume
- 11
- Pages
- 595635-595635
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC7770114
- OpenAlex
- W3112818719
- Cited by
- 129
- References
- 240
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 21 · 2023: 35 · 2022: 30 · 2021: 11
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Consejo Nacional de Ciencia y Tecnología (2019-2020)
- Benemérita Universidad Autónoma de Puebla (VIEP-BUAP 2019)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- cannabidiol, Parkinson's disease, neuroprotection, neuromodulation, endocannabinoid system, basal ganglia, nigrostriatal pathway, CB1 receptor, CB2 receptor, TRPV1 receptor, PPARγ, GPR55, GPR3, GPR6, GPR18, GPR30, GPR31, GPR34, GPR35, GPR37, GPR39, GPR40, GPR41, GPR
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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